Abstract: The primary goal of this COBRE is to strengthen the biomedical research infrastructure in Louisiana by training Promising Junior Investigators (PJIs) who can develop independent research addressing a major health problem in our region. Virus-associated cancers remain a major cause of morbidity and mortality in our region and disproportionately affect the African American population. These include HPV- associated cervical, anogenital, and head and neck cancers, KSHV-associated Kaposi sarcoma and primary effusion lymphoma, HCV- and HBV-associated liver cancers and others, all which are unusually highly prevalent in our area. Increases in these diseases may be explained, in part, by the large number of HIV-infected patients in the region. In addition, our data also indicate that co-infection of cells with more than one virus promotes or associates with malignant transformation. Therefore, understanding how particular viruses and viral co- infections promote the development of malignancies is essential to identifying and implementing new preventative, diagnostic and treatment strategies. It follows that training a new cadre of investigators capable of conducting novel research in the field of viral oncology is essential for our state. This will be accomplished by developing a Center for Translational Viral Oncology (CTVO) that leverages existing resources in order to train new investigators, develops novel laboratory infrastructure, and supports research projects designed to study these diseases in our unique populations. The CTVO will support the scientific, mentoring and administrative needs of the PJIs by providing (i) experienced mentoring teams composed of NIH-funded and internationally recognized investigators who are committed to guiding PJIs in developing cutting edge research, ensuring their successful training, and supporting their development as independent researchers; (ii) unique clinical material from high risk patient populations ? PJIs will have preferential access to a unique (and increasing) set of clinically annotated biospecimens from HIV+ and HIV- patients with virus-associated cancers collected at the University Medical Center ? New Orleans (iii) well-established administrative and cutting edge scientific infrastructure including integrated cancer and HIV clinical trials programs to translate the findings of these projects, advanced core research laboratories, and a new expanded and unique biorepository, the HIV/Clinical Tumor Biorepository (HCTB) Core. Initially, this COBRE brings four projects led by PJIs to study the role of oncogenic viruses such as HPV, KSHV and EBV, as well as, viruses of increasing interest in human carcinogenesis such as human cytomegalovirus (HCMV), human endogenous retrovirus sequences (HERVs), and human neurotropic Polyomavirus JC (JCV). These cancers arise more commonly in the setting of immune deficiencies (including HIV infection), and disproportionately affect African American patients in Louisiana. Implementation of the proposed work will be directed by the following Specific Aims: 1) to establish interdisciplinary teams of investigators and laboratory core infrastructure to support PJI-led research projects on virus-host interactions and their role in pathogenesis of cancer; 2) to develop an administrative infrastructure to mentor and promote the independent career of the PJIs; and 3) to leverage institutional NIH-funded Centers and Programs at the participating institutions to facilitate the integration of PJIs within the clinical and translational research infrastructure. The completion of this program will provide this region with enhanced capabilities to address these and other virus related health problems that may arise in the future.